Tafasitamab + Lenalidomide/ICE for Large B-Cell Lymphoma

Overseen By Aubree Dendorfer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: David Bond, MD

Must not be taking: Anti-CD19, Lenalidomide

Disqualifiers: CNS involvement, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8-16 weeks

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of medications to treat large B-cell lymphoma that has returned or not responded to previous treatments. It examines the effectiveness of tafasitamab (an antibody that may stop cancer cells from growing), lenalidomide (which may prevent cancer growth), and a chemotherapy regimen called ICE. Suitable candidates for this trial include those who have already tried one type of chemo-immunotherapy and have relapsed or refractory large B-cell lymphoma. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from innovative therapies.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, prior lymphoma therapy should be completed more than two weeks before starting the trial, except for corticosteroids used for symptom relief.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of tafasitamab and lenalidomide was tested for safety in patients with large B-cell lymphoma. Among 156 patients with safety data, 54% experienced at least one significant side effect during treatment. While the treatment can be effective, some patients might encounter side effects. Discussing these potential side effects with a doctor is important to understand their implications. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tafasitamab and lenalidomide for treating large B-cell lymphoma because it introduces a novel approach compared to existing options like R-CHOP, which typically involve rituximab and chemotherapy agents. Tafasitamab is a monoclonal antibody that specifically targets CD19 on the surface of cancer cells, potentially improving the precision and effectiveness of treatment. Meanwhile, lenalidomide enhances the immune system's response against cancer cells, working synergistically with tafasitamab. This combination aims to offer a more targeted and potentially more effective treatment for patients who may not fully respond to conventional therapies.

What evidence suggests that this trial's treatments could be effective for large B-cell lymphoma?

In this trial, participants will receive a combination of tafasitamab and lenalidomide, followed by an ICE regimen, which includes chemotherapy drugs such as carboplatin, etoposide, and ifosfamide. Research has shown that tafasitamab, when combined with lenalidomide, may help treat large B-cell lymphoma that is difficult to treat or has recurred. Tafasitamab, a monoclonal antibody, can stop cancer cells from growing and spreading. Lenalidomide is known for blocking tumor growth. Studies have demonstrated that using these drugs together can be effective, especially when followed by the ICE regimen. This combination aims to kill cancer cells and prevent their spread. Although this approach is still under study, early results suggest it could be a strong option for patients whose lymphoma has not responded to other treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

David A. Bond, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with certain types of large B-cell lymphoma that has relapsed or hasn't responded to treatment. They must have had one prior chemo-immunotherapy, be eligible for a transplant, and able to consent. Participants need adequate organ function and no history of significant heart disease, uncontrolled infection, or other cancers that could interfere.

Inclusion Criteria

Serum total bilirubin =< 1.5 x upper limit of normal (ULN) (except in patients with Gilbert Syndrome who can have total bilirubin < 3.0 mg/dL)

My hemoglobin level is at least 8.0 g/dL, unless it's low due to my lymphoma.

My diagnosis is a specific type of advanced B cell lymphoma.

Exclusion Criteria

Known contraindication to any medication in the treatment plan, including known hypersensitivity

I finished my lymphoma treatment over two weeks ago, except for steroids for symptom relief.

My lymphoma has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tafasitamab IV, lenalidomide PO, etoposide IV, ifosfamide IV, and carboplatin IV. Imaging and blood sample collection are conducted throughout the study.

8-16 weeks

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival after treatment.

Up to 2 years

Long-term follow-up

Participants are monitored for overall survival and incidence of adverse events.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Etoposide
• Ifosfamide
• Lenalidomide
• Tafasitamab

Trial Overview The study tests tafasitamab plus lenalidomide followed by ICE chemotherapy (carboplatin, etoposide, ifosfamide) as salvage therapy in patients suitable for transplants. Tafasitamab is an antibody against cancer cells; lenalidomide may block tumor growth; ICE kills or stops cancer cell division.

How Is the Trial Designed?

Group I: Treatment (tafasitamab, lenalidomide, ICE regimen) Experimental Treatment 9 Interventions

Patients receive tafasitamab IV, lenalidomide PO, etoposide IV, ifosfamide IV and carboplatin IV on study. Patients undergo PET or CT, and undergo blood sample collection throughout the study. Patients may undergo tissue biopsy on study.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

David Bond, MD

Lead Sponsor

Trials

4

Recruited

110+

Published Research Related to This Trial

Lenalidomide is an orally bioavailable immunomodulator that has shown significant antitumor activity in treating various types of B-cell lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma.

The drug has a favorable safety profile and is effective both as a standalone treatment and in combination with other therapies, marking a shift from traditional chemotherapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. Galanina, N., Petrich, A., Nabhan, C.[2019]

In the phase II L-MIND study, tafasitamab combined with lenalidomide showed a 57.5% objective response rate in patients with relapsed/refractory diffuse large B-cell lymphoma, with a complete response in 40% of patients after more than 35 months of follow-up.

The treatment demonstrated a median overall survival of 33.5 months and a median duration of response of 43.9 months, with no unexpected toxicities, indicating a favorable safety and efficacy profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Duell, J., Maddocks, KJ., González-Barca, E., et al.[2021]

Tafasitamab, an anti-CD19 monoclonal antibody, received accelerated approval in July 2020 for treating adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in combination with lenalidomide, marking it as the first second-line therapy approved for this patient group in the USA.

The drug is administered intravenously at a recommended dose of 12 mg per kg and is also being explored for use in other B-cell malignancies, indicating its potential versatility in treating various types of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab: First Approval. Hoy, SM.[2022]

In a phase 2 study involving 81 patients with relapsed or refractory diffuse large B-cell lymphoma, the combination of tafasitamab and lenalidomide resulted in a 60% objective response rate, with 43% achieving a complete response, indicating significant antitumor activity.

The treatment was generally well tolerated, although serious adverse events occurred in 51% of patients, with neutropenia being the most common, suggesting that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Salles, G., Duell, J., González Barca, E., et al.[2020]

A 75-year-old man with high-risk transformed Waldenström macroglobulinemia (WM) showed a complete and durable response to tafasitamab plus lenalidomide (TAF/LEN), indicating potential efficacy for this combination therapy in treating transformed WM.

This case suggests that TAF/LEN, which is approved for relapsed diffuse large-cell lymphoma, may also be a promising and tolerable treatment option for patients with transformed WM, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transformed Waldenström Macroglobulinemia Responsive to Tafasitamab Plus Lenalidomide: A Case Report. Nasir, SA., Pandya, D., Wojkiewicz, S., et al.[2023]

In the final 5-year analysis of the L-MIND study involving 80 patients with relapsed/refractory diffuse large B-cell lymphoma, the combination of tafasitamab and lenalidomide showed a significant objective response rate of 57.5%, with a complete response rate of 41.3%.

The treatment demonstrated long-term clinical benefits, with a median overall survival of 33.5 months and manageable adverse events, indicating that this immunotherapy combination is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety in the phase II L-MIND study. Duell, J., Abrisqueta, P., Andre, M., et al.[2023]

Tafasitamab plus lenalidomide (TAFA + LEN) showed significantly better overall survival (OS) and progression-free survival (PFS) compared to standard treatments like polatuzumab vedotin + bendamustine + rituximab (POLA + BR) and bendamustine + rituximab (BR) in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL).

The study found that TAFA + LEN was associated with longer duration of response (DOR) and higher complete response rates (CRR), indicating its potential as a more effective treatment option, although further validation through large randomized trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tafasitamab Plus Lenalidomide Versus 3 Rituximab-Based Treatments for Non-Transplant Eligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Matching-Adjusted Indirect Comparison. Cordoba, R., Prawitz, T., Westley, T., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05821088?term=AREA%5BConditionSearch%5D(%22Hodgkin's%20Paragranuloma%22)%20AND%20AREA%5BInterventionSearch%5D(%22Isophosphamide%20mustard%22)&rank=9

NCT05821088 | Tafasitamab and Lenalidomide Followed ... Evaluate the anti-tumor activity of tafasitamab and lenalidomide followed by tafasitamab and ICE as first salvage therapy for relapsed/ refractory large B cell ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02612

Tafasitamab and Lenalidomide followed by ... This phase II clinical trial evaluates tafasitamab and lenalidomide followed by tafasitamab and the carboplatin, etoposide and ifosfamide (ICE) regimen as ...

3. withpower.com withpower.com/trial/phase-2-lymphoma-4-2023-0b447

Tafasitamab + Lenalidomide/ICE for Large B-Cell Lymphoma This phase II clinical trial evaluates tafasitamab and lenalidomide followed by tafasitamab and the carboplatin, etoposide and ifosfamide (ICE) regimen as ...

4. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/diffuse-large-b-cell-lymphoma

Diffuse Large B-Cell Lymphoma Clinical Trials The purpose of this study is to assess the side effects and best dose of lenalidomide when given together with rituximab-ifosfamide-carboplatin-etoposide (R-ICE) ...

5. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601733/

Clinical Review - Tafasitamab (Minjuvi) - NCBI Bookshelf Although the cure rate of DLBCL is high, approximately 30% to 50% of patients in Canada experience relapsed or refractory (R/R) disease after treatment with ...

6. ashpublications.org ashpublications.org/blood/article/142/26/2327/498041/Tafasitamab-and-lenalidomide-in-large-B-cell

Tafasitamab and lenalidomide in large B-cell lymphoma Of all patients, 156 had safety data available, of whom 54% had at least 1 clinically significant AE during treatment (supplemental Table 2).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8409029/

Long-term outcomes from the phase II L-MIND study of ... To further determine the long-term clinical efficacy and safety of tafasitamab plus lenalidomide treatment in patients with R/R DLBCL, we provide updated data ...

8. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-late-breaking-tafasitamab-monjuvir-data-ash-2024

Incyte Late-Breaking Tafasitamab (Monjuvi®) Data at ASH ... “In the Phase 3 inMIND trial, tafasitamab demonstrated impressive efficacy and safety for treating certain patients with follicular lymphoma, ...